Through its interaction with receptors borne on neuronal and other cells, 5-hydroxytryptamine (5-HT; serotonin), exerts various physiological effects. Imbalances in this interaction are believed responsible for such conditions as anxiety, depression, hallucination, migraine, chemotherapy-induced nausea, and for disorders in sexual activity, cardiovascular activity and thermoregulation, among others. From an improved understanding of the 5-HT receptor population, it is apparent that these effects are mediated selectively through individual types and sub-types of 5-HT receptors.
Migraine, for example, has been treated with ergotamine, dihydroergotamine and methysergide, all of which act at 5-HT1 type receptors. Their use is associated with undesirable side effects, however, likely because they interact also with various other 5-HT receptor types. An improved side effect profile is seen with the more recently marketed tryptamine analog known as sumatriptan, which binds somewhat selectively at the 5-HT1 receptor sub-type known as 5-HT1D (see Glennon and Westkaemper, DN&P, 1993, 6 (6):390) .
Given the physiological and clinical significance of the 5-HT1D receptor, it would be desirable to provide compounds capable of binding tightly and selectively to this receptor, for medical use for example to treat indications such as migraine and others for which administration of a 5-HT1D ligand is indicated, and also for research and diagnostic use for example to identify these receptors and to screen for drug candidates.